Nutrition advice often recommends various diets, but significant gaps remain in understanding how nutrients affect individual cells. Research led by UCLA scientist Tara TeSlaa, supported by an NIH Director’s New Innovator Award, aims to address this gap by developing a method to record nutrient usage in specific cell types within their natural environment.
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TeSlaa explains that cell metabolism is not static; it adapts based on factors like diet and disease, which influences cellular behavior. Current nutrition research often associates nutrients with health outcomes without clarifying cellular processes, leading to conflicting results. For instance, one study may suggest dietary fat is beneficial, while another may indicate it is harmful. TeSlaa emphasizes that nutrients beneficial for one cell type might not be for another.
The NIH award provides up to $2.375 million over five years to facilitate this innovative research. One of the main challenges met by metabolism researchers is that metabolites—molecules formed when cells process nutrients—can change rapidly, complicating studies. Isolating specific cell types often alters their metabolic conditions, making it challenging to obtain accurate measures of nutrient use.
TeSlaa's lab employs a technique called STOMP (Stable Isotope Tracing of Orthogonal Metabolites into bioPolymers), which marks nutrients with stable isotopes. This allows researchers to trace how these nutrients are incorporated into more stable molecules like proteins and DNA over time, creating a lasting record of nutrient use. Mass spectrometry can then analyze these records after cells are isolated.
The research will initially focus on the liver and pancreas, vital to understanding metabolic diseases like diabetes. While the liver regulates overall metabolism, the pancreas's beta cells sense blood glucose and secrete insulin, making their study crucial but challenging due to their limited presence in the organ.
TeSlaa's goal is to establish a resource detailing nutrient usage across different cell types and conditions, shedding light on metabolic advantages for various cells. This granular view can also help highlight less abundant yet significant cell types involved in critical bodily functions, particularly during tissue damage.
The project has broader implications for identifying how laboratory models replicate metabolic processes in the human body. TeSlaa plans to compare traditional models, such as tissue slices and stem cell-derived organoids, with mouse studies to determine which best reflects natural metabolic behaviors, particularly for muscle stem cells that have yet to be studied thoroughly in their native environment.
Ultimately, TeSlaa envisions the metabolic map as a first step in deciphering cellular metabolism, contributing to a better understanding of how nutrient utilization shifts with factors like aging and exercise.